Quantitative measurements in obstetric MRI

This thesis describes the development and application of quantitative echo planar magnetic resonance imaging techniques to the study of human placental development in normal and compromised pregnancies. Initially, a method of rapidly and accurately measuring the transverse relaxation time is proposed using a multi-echo measurement sequence. The method is described, validated on CUS04 phantoms and applied in the study of the human placenta and gastric dilution. It is shown that the inversion provided by sinc pulsesis insufficient to generate an accurate measurement but using adiabatic refocusing pulses yields a measurement that is comparable with a single spin echo. Subsequently, a rapid magnetisation transfer method is presented that allows the quantification of the relative size of the bound proton pool. An experimental pulse sequence is proposed, along with a theoretical model, that permits the investigation of the bound proton pool's transition towards the steady state. The sequence and model are validated using agar gel phantoms and shown to agree well with literature values. When applied in the study of the human placenta, it is shown that there is no significant variation in the fitted value of the bound proton pool size with increasing gestational age or in compromised pregnancies. Finally, several methods of measuring the oxygenation level of blood within the human placenta are investigated. The signal intensities of cardiac gated T~• and T~ weighted images acquired at various points in the maternal cardiac cycle are explored but no significant variation is shown through the cycle. A pulsed gradient spin echo sequence that utilises anti-symmetric sensitising gradients is validated and then applied in the human placenta. Oxygenation measurements with this technique are shown to be unfeasible but the potential of the sequence to monitor blood flow in the placenta is demonstrated

Quantitative measurements in obstetric MRI

This thesis describes the development and application of quantitative echo planar magnetic resonance imaging techniques to the study of human placental development in normal and compromised pregnancies. Initially, a method of rapidly and accurately measuring the transverse relaxation time is proposed using a multi-echo measurement sequence. The method is described, validated on CUS04 phantoms and applied in the study of the human placenta and gastric dilution. It is shown that the inversion provided by sinc pulsesis insufficient to generate an accurate measurement but using adiabatic refocusing pulses yields a measurement that is comparable with a single spin echo. Subsequently, a rapid magnetisation transfer method is presented that allows the quantification of the relative size of the bound proton pool. An experimental pulse sequence is proposed, along with a theoretical model, that permits the investigation of the bound proton pool's transition towards the steady state. The sequence and model are validated using agar gel phantoms and shown to agree well with literature values. When applied in the study of the human placenta, it is shown that there is no significant variation in the fitted value of the bound proton pool size with increasing gestational age or in compromised pregnancies. Finally, several methods of measuring the oxygenation level of blood within the human placenta are investigated. The signal intensities of cardiac gated T~• and T~ weighted images acquired at various points in the maternal cardiac cycle are explored but no significant variation is shown through the cycle. A pulsed gradient spin echo sequence that utilises anti-symmetric sensitising gradients is validated and then applied in the human placenta. Oxygenation measurements with this technique are shown to be unfeasible but the potential of the sequence to monitor blood flow in the placenta is demonstrated

Optimal flip angles for in vivo liver 3D T1 mapping and B1+ mapping at 3T.

Purpose The spoiled gradient recalled echo (SPGR) sequence with variable flip angles (FAs) enables whole liver T1 mapping at high spatial resolutions but is strongly affected by B1+ inhomogeneities. The aim of this work was to study how the precision of acquired T1 maps is affected by the T1 and B1+ ranges observed in the liver at 3T, as well as how noise propagates from the acquired signals into the resulting T1 map. Theory The T1 variance was estimated through the Fisher information matrix with a total noise variance including, for the first time, the B1+ map noise as well as contributions from the SPGR noise. Methods Simulations were used to find the optimal FAs for both the B1+ mapping and T1 mapping. The simulations results were validated in 10 volunteers. Results Four optimized SPGR FAs of 2°, 2°, 15°, and 15° (TR = 4.1 ms) and B1+ map FAs of 65° and 130° achieved a T1 coefficient of variation of 6.2 ± 1.7% across 10 volunteers and validated our theoretical model. Four optimal FAs outperformed five uniformly spaced FAs, saving the patient one breath-hold. For the liver B1+ and T1 parameter space at 3T, a higher return in T1 precision was obtained by investing FAs in the SPGR acquisition rather than in the B1+ map. Conclusion A novel framework was developed and validated to calculate the SPGR T1 variance. This framework efficiently identifies optimal FA values and determines the total number of SPGR and B1+ measurements needed to achieve a desired T1 precision

Compartment-based reconstruction of acquisition-weighted 31P cardiac MRSI reduces sensitivity to cardiac motion and scan planning

Motivation:31P magnetic resonance spectroscopic imaging (31P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure in vivo, allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac 31P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction.Methods: Six healthy volunteers were scanned twice in a test–retest procedure to allow quantification of repeatability. Each scan consisted of anatomical localizers and two acquisition-weighted (AW) 31P MRSI acquisitions, which were acquired with and without cardiac gating. Five patients with heart failure with a preserved ejection fraction were then scanned with the same 31P MRSI sequence without cardiac gating. All 31P MRSI datasets were reconstructed with both conventional Fourier transform (FT)-based reconstruction and SLAM reconstruction, which were compared statistically. The effect of shifting the 31P MRSI acquisition field of view was also investigated.Results: In the healthy volunteer cohort, the spectral fit of the SLAM reconstructions had significantly improved Cramer–Rao lower bounds (CRLBs) compared to the FT-based reconstruction of non-cardiac gated data, as well as improved coefficients of variability and repeatability. The SLAM reconstruction found a significant difference in the PCr/ATP ratio between the healthy volunteer and patient cohorts, which the FT-based reconstruction did not find. Furthermore, the SLAM reconstruction was less influenced by the placement of the field of view (FOV) of the 31P MRSI acquisition in post hoc analysis.Discussion: The experimental benefits of the SLAM reconstruction for AW data were demonstrated by the improvements in fit confidence and repeatability seen in the healthy volunteer cohort and post hoc FOV analysis. The benefit of SLAM reconstruction of AW data for clinical studies was then illustrated by the patient cohort, which suggested improved sensitivity to clinically significant changes in the PCr/ATP ratio

A 3D-Hybrid-Shot Spiral Sequence for Hyperpolarized 13^{13}C Imaging

Purpose: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral-Spatial RF excitation has been shown to form an attractive magnetization-efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. Methods: In this work we propose a novel 3D hybrid-shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction. Results: We have implemented this sequence, both via simulation and on a pre-clinical scanner, to demonstrate its feasibility, in both a 1H phantom and with hyperpolarized 13C pyruvate in vivo. Conclusion: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation

Compartment-based reconstruction of 3D acquisition-weighted 31P cardiac magnetic resonance spectroscopic imaging at 7 T: a reproducibility study

Even at 7 T, cardiac 31P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal-to-noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment-based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment-based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5-min 3D acquisition-weighted (AW) cardiac 31P phase encode-based MRSI acquisition and two 6.5-min truncated k-space acquisitions with increased averaging (4 × 4 × 4 central k-space phase encodes and fractional SLAM [fSLAM] optimized k-space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition–reconstruction combinations. The phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment-based reconstruction algorithms with the AW 31P acquisition resulted in a significant increase in SNR compared with previously published Fourier-based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k-space performed no better than the common AW approach. Compartment-based spectroscopy approaches provide an attractive reconstruction method for cardiac 31P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k-space sampling strategy

In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy

Aims The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice. Methods and Results Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy. Conclusions MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases

Model-assisted measurements of suspension-feeding flow velocities

Benthic marine suspension feeders provide an important link between benthic and pelagic ecosystems. The strength of this link is determined by suspension-feeding rates. Many studies have measured suspension-feeding rates using indirect clearance-rate methods, which are based on the depletion of suspended particles. Direct methods that measure the flow of water itself are less common, but they can be more broadly applied because, unlike indirect methods, direct methods are not affected by properties of the cleared particles. We present pumping rates for three species of suspension feeders, the clams Mya arenaria and Mercenaria mercenaria and the tunicate Ciona intestinalis, measured using a direct method based on particle image velocimetry (PIV). Past uses of PIV in suspension-feeding studies have been limited by strong laser reflections that interfere with velocity measurements proximate to the siphon. We used a new approach based on fitting PIV-based velocity profile measurements to theoretical profiles from computational fluid dynamic (CFD) models, which allowed us to calculate inhalant siphon Reynolds numbers (Re). We used these inhalant Re and measurements of siphon diameters to calculate exhalant Re, pumping rates, and mean inlet and outlet velocities. For the three species studied, inhalant Re ranged from 8−520, and exhalant Re ranged from 15−1073. Volumetric pumping rates ranged from 1.7−7.4 l h−1 for Mya, 0.3−3.6 l h−1 for Mercenaria, and 0.07−0.97 l h−1 for Ciona. We also used CFD models based on measured pumping rates to calculate capture regions, which reveal the spatial extent of pumped water. Combining PIV data with CFD models may be a valuable approach for future suspension-feeding studies

The effects of iodinated CT contrast agent on phosphorus MRS

Synopsis Contrast-enhanced CT examination can influence H-MRI measurements performed within 24h after the CT scan, due to a reduction in water T and T caused by the iodinated contrast agents used in CT. We have investigated whether contrast from a previous CT examination would also influence metabolic measurements made using P-MRS, by measuring the T of H and P signals in human blood. We find that iodinated CT contrast agent has no effect on phosphorus T s. Therefore, P-MRS examinations will not be influenced by prior CT (unlike H-MRI scans).We acknowledge financial support from the British Heart Foundation (FS/10/002/28078; FS/14/17/30634; RG/11/9/28921), a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (098436/Z/12/Z), a Novo Nordisk Foundation Postdoctoral Research Fellowship and from the Slovak Grant Agencies VEGA (2/0001/17) and APVV (15-0029)